Neural Regeneration Research ›› 2015, Vol. 10 ›› Issue (4): 589-593.doi: 10.4103/1673-5374.155432

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Enhancing hippocampal blood flow after cerebral ischemia and vasodilating basilar arteries: in vivo and in vitro neuroprotective effect of antihypertensive DDPH

Li Sun 1, 2, Qin Li 3, Wei-ting Wang 2, Yu-hua Chen 1,  Lian-jun Guo 2   

  1. 1 Department of Neurology, Wuhan Brain Hospital (General Hospital of the Yangtze River Shipping), Wuhan, Hubei Province, China
    2 Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province, China
    3 Department of Pharmacology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
  • Received:2015-03-16 Online:2015-04-22 Published:2015-04-22
  • Contact: Yu-hua Chen, whchyh@163.com.
  • Supported by:

    This study was financially supported by grants from the National Natural Science Foundation of China, No. 81173038; Yangtz River Navigational Matters Authority of Ministry of Transport of China, No. 201210011; and Clinical Medicine Research Program of Wuhan Health Planning Commission of China, No. WX14D12.

Abstract:

1-(2,6-Dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)-propane hydrochloride (DDPH) is a novel antihypertensive agent based on structural characteristics of mexiletine and verapamine. We investigated the effect of DDPH on vasodilatation and neuroprotection in a rat model of cerebral ischemia in vivo, and a rabbit model of isolated basilar arteries in vitro. Our results show that DDPH (10 mg/kg) significantly increased hippocampal blood flow in vivo in cerebral ischemic rats, and exerted dose-dependent relaxation of isolated basilar arteries contracted by histamine or KCl in the in vitro rabbit model. DDPH (3 × 10–5 M) also inhibited histamine-stimulated extracellular calcium influx and intracellular calcium release. Our findings suggest that DDPH has a vasodilative effect both in vivo and in vitro, which mediates a neuroprotective effect on ischemic nerve tissue.

Key words: nerve regeneration, DDPH, cerebral ischemia, hippocampus, blood flow, isolated basilar artery, dose-response curve, NSFC grant, neural regeneration